X-Dimer Mutations and their Effects on the Folding Stability and Assembly of ECAD12 at the K14-D138 Interface

Coghlan, Martha Kaitlyn (2015) X-Dimer Mutations and their Effects on the Folding Stability and Assembly of ECAD12 at the K14-D138 Interface. Undergraduate thesis, under the direction of Susan Pedigo from Chemistry and Biochemistry, University of Mississippi.

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Abstract

Classical cadherins were first identified by their function in mediating calcium-dependent cellular adhesion and constitute a large family of cellular adhesion receptor proteins whose differential binding is central to the development and maintenance of tissue architecture. The interface underlying the binding interaction reveals that all classical cadherins share a common adhesive interface in which the portion of the β-A strand closest to the N-terminus is swapped between EC1 domains of the adhesive partner protomers. A second dimeric configuration, known as the ‘X-dimer’, is the face-to-face association of two protomers in which their orientation is dictated by three symmetrical noncovalent interactions facilitated by residues near the calcium-binding sites between EC1 and EC2. This thesis addresses a specific hypothesis regarding the role of K14 in the orientation of the protomers in the X-dimer structure. Structural and functional characterization experiments on mutants of K14 including Gel Imaging, Ultraviolet Absorbance, Temperature Denaturation Studies, and Liquid Chromatography, offer significant insight on the role of K14 in the kinetics of dimerization of wildtype E-cadherin. Data presented in the current studies indicate that the identity of the residue in the fourteenth position affects the kinetics and equilibria of dimerization by E-cadherin. The overarching conclusion is that the loss of K14 is deleterious to the function of E-cadherin.

Item Type: Thesis (Undergraduate)
Creators: Coghlan, Martha Kaitlyn
Student's Degree Program(s): B. A. Biochemistry
Thesis Advisor: Susan Pedigo
Thesis Advisor's Department: Chemistry and Biochemistry
Institution: University of Mississippi
Subjects: Q Science > QD Chemistry
Depositing User: Martha Kaitlyn Coghlan
Date Deposited: 19 May 2015 20:24
Last Modified: 23 Oct 2015 19:13
URI: http://thesis.honors.olemiss.edu/id/eprint/463

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